Sensitivity always trumps specificity in every disorder in DSM5 No axes (as determined by APA) All disorders must have severity indices (as per APA)
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1 Sensitivity always trumps specificity in every disorder in DSM5 No axes (as determined by APA) All disorders must have severity indices (as per APA) No specification of research standards or methods General interest in dimensions but no agreement about what they should be or how to measure them For ICD 11, commitment to primary care
2 Do not to change who is included Make the framework more useful for all ages and genders, all developmental levels and all degrees of severity where there is impairment Make sure that the criteria do describe ASD and don t describe many people who don t have ASD Allow separate ways of describing behaviors and noting etiology and associated conditions
3 Scientific validity Questioning the importance of very early language milestones vs. fluent speech in older years Overlap in research when VIQ controlled Concern about access to services
4 ADI-R RRB Domain Scores
5 ASD Distribution of Probands 100 Total Probands = Autism PDD-NOS Aspergers Percent N = sample size F = % Females A = Mean Age 10 0 aa ac ad ae af ag ah ai aj ak am N=32 F=6.3% N=28 F=17.9% N=59 F=11.9% N=61 F=11.5% N=62 F=12.9% N=52 F=9.6% N=22 F=27.3% N=24 F=16.7% N=30 F=13.3% N=24 F=8.3% N=29 F=17.2% Site
6 AUT AUT < 85 VIQ > 86 a, c, g, h, i, j AUT AUT Site b, d, e, f, k, l AUT > 5 < 4 ADOS-RRB < 102 VIQ > 103 AUT PDD AUT PDD PDD > 15 ADI < 14 AUT ASP > 12 ADI-Soc < 11 > 6 CSS < 5 Soc < 122 NVIQ >123 c, i Site a, f AUT PDD AUT PDD PDD ASP PDD PDD > 21 ADI- AUT ASP < 93 VIQ > 94 VComm < 20 ADI- > 20 < 29 > 7 CSS < 6 VComm AUT PDD AUT PDD AUT PDD AUT PDD > 3 < 7 PDD CSS > 8 N=2102 > 12 ADOS Soc + Comm < 11 AUT g AUT AUT Site AUT a, c, f, i AUT Diagnostic, Site, Demo, Diagnostic AUT a, c, f, g, i b, d, e, h, j, k, l Site ADOS RRB < 2 AUT < 115 PDD < 70 VABC < 2 PDD > 71 VIQ ABC Hyper > 3 AUT PDD < 8y0m > 116 ASP Age > 8y1m ASP The Simons Simplex Collection Lord et al. (2012)
7 a b c d e f h i l k Predictors of various ASD diagnoses by site 1 st split a b c d e f h i l k VIQ VIQ Vineland ADOS Soc+Com CSS ADOS SocAff VIQ ADI NV- Comm ADOS ADOS VIQ Soc+Com Soc+Com ADOS Soc+Com ADOS RRB ADOS Soc+Com ADOS CSS CSS Soc+Com VIQ ADOS RRB ADOS SocAff VIQ ADOS RRB VIQ ADOS Soc+Com ADOS Soc+Com ADOS Soc+Com ADOS SocAff ADOS Soc+Com CSS VIQ ADOS Soc+Com Vineland ADOS RRB VIQ VIQ NVIQ NVIQ Mat Educ ADOS Mod VIQ ADI Social ADOS Soc+Com ADOS RRB ADOS Mod VIQ CSS CSS NVIQ ADOS Mod VIQ a b c d e f h i l k 2 nd split ADOS RRB NVIQ ADI RRB CSS ADOS RRB ADOS RRB ADOS Mod Vineland ADOS RRB NVIQ Vineland NVIQ CSS ADOS Soc+Com CSS NVIQ ADOS Mod ADOS RRB ADOS Mod ADOS RRB NVIQ ADOS Soc+Com ADOS Soc+Com ADOS Mod Vineland VIQ VIQ VIQ ADOS RRB CSS ADI Social ADOS Soc+Com ADI NV- Comm NVIQ ADI Social CSS ADI RRB NVIQ CSS CSS VIQ ADOS Mod VIQ ADOS Soc+Com ADOS Soc+Com ADOS RRB ADI Social VIQ ADOS RRB ADOS Mod
8 That people with diagnoses of Asperger Syndrome or PDD- NOS do not lose services because of being included in ASD That people who prefer the term Asperger Syndrome to refer to themselves can use it That the ranges of skill levels and abilities within ASD are not underestimated
9 Social communication Fixated interests and repetitive behaviors (RRBs)
10 Social Communication Fixated Interests & Repetitive Behaviors Expressive Language Level/Cognitive Level
11 TITLE Deficits in social-emotional reciprocity Deficits in nonverbal communicative behaviors used for social interaction Deficits in developing and maintaining relationships and adjusting behavior to social contexts, appropriate to developmental level
12 ADOS Module 3 Dimensions (N=245) Basic social communication Items Descriptive gestures.82 Unusual eye contact.74 Advanced/ Reciprocal social interaction Restricted repetitive behaviors Facial expressions.83 Shared enjoyment Quality of social overtures Conversation.57 Quality of social response Amount of reciprocal social communication.74 Overall quality of rapport Stereotyped speech.94 Mannerisms.38 Excessive interest Χ 2 (42)=49.25, p=.206; RMSEA=.027; CFI=1.0 Bishop, Havdahl, et al. (2016).72
13 TIReRRTLE A. Stereotyped or repetitive speech, motor movements or use of objects B. Excessive adherence to routines, ritualized patterns of verbal or nonverbal behavior or excessive resistance to change C. Highly restricted, fixated interests that are abnormal in intensity or focus D. Hyper- or hypo-reactivity to sensory input or unusual interest in sensory aspects of environment
14 Mostly much simpler But we still have some frustrating situations: Circumstances for very young children Very difficult to make diagnoses in very, very young children (children who are not yet walking, children under 12 months of age) but it is possible some times Children and adults with very, very limited language or limited mobility are more difficult to diagnose The requirement that, to have autism, a person has to have an impairment of some sort (this can be self declared)
15 Parent or caregiver report Structured questionnaires Less structured interviews and packets Structured interviews Teachers and therapists Questionnaires and packets Phone calls Observation and self-report Interview of the patient or AQ ADOS WHAT DO YOU WANT THE EVALUATOR TO KNOW ABOUT YOUR CHILD in each of the areas above (social communication; RRB s?)
16 Normal variation Maybe awkward or isolated but WNL WNL for developmental level and no interference Dimensional Ratings for DSM 5 ASD Social Communication Fixated Interests and Repetitive Behaviors Requires very substantial support Minimal social communication Marked interference in daily life Requires substantial support Marked deficits with limited initiations and reduced or atypical responses Obvious to the casual observer and occur across context Requires some support Even with support, noticeable impairments Significant interference in at least one context Subclinical symptoms Some symptoms in this or both domains; no significant impairment Unusual or excessive but no interference
17 6. Specifiers: With the new criteria, if the child has ASD symptoms, he or she gets an ASD diagnosis with a specifier for the etiology or associated medical condition: ASD with Rett Syndrome ASD with Fragile X ASD with 15q11-13 Or ASD with tonic-clonic seizures ASD with chronic irritable bowel syndrome
18 Onset should be in early childhood DSM5 explicitly acknowledges that recognition is different than onset CAN T have a clearly negative history into later childhood CURRENT IMPAIRMENT must be present though impairment is quantified by level of support needed 6 7
19 Age of perceived onset Pattern of onset (regression/no loss) Examples: ASD with onset before 18 months and loss of words and social skills ASD with onset by age 30 months and loss of social skills ASD with no clear onset and no loss
20 Intellectual disabilities Communication and language disorders Attention deficits and/or hyperactivity Mood disorders Oppositional behavior 9. There are now levels of severity for each diagnosis in DSM 5.
21 9. Pragmatic (Social) Communication Disorder (PSCD) 1) is an impairment of pragmatics, only diagnosed when ASD is ruled out 2) diagnosed based on difficulty in the social uses of verbal and nonverbal communication in naturalistic contexts, 3) which affects the development of social relationships and discourse comprehension and 4) cannot be explained by low abilities in the domains of word structure and grammar or general cognitive ability.
22 Prioritizing sensitivity makes sense but has some dangers Diagnostic criteria for disorders are not the same as a family receiving an adequate diagnosis Measuring outcomes and response to treatments is hard (and not same as dx)
23 Role of existing instruments ADOS now has separable dimensions through the comparison/severity scores across modules Looking at combinations of ADOS and other measures (SRS, SCQ, new interview-asi) ADI-R (long caregiver interview), soon to be revised; Can still be tremendously helpful for working with a family Does provide quantitative measures of separate dimensions beyond the ADOS More affected by expectations and knowledge
24 Verbal IQ in autism is not stable in young children. Many children with autism will be very delayed in language at age 2, and begin to improve by 3, remain delayed through school age, but have good spoken language by adolescence. Nonverbal IQ is more stable, but still may change. In most cases, children who have high nonverbal IQs when they are young (2 or 3), continue to do so into adulthood, unless they do not develop language. Children with very low IQs (under 30) even when young, often remain very delayed, but not always.
25 1. There are many ways to do this. Some tests are much more appropriate to be used with people with ASD. Sometimes examiners are not familiar with these tests or do not have access to them and then parents need to stick up for themselves and getting access to these tests and examiners. 2. Verbal skills should be separated from nonverbal skills. Expressive language (e.g, speaking or communicating) should be assessed separately from receptive language (e.g., understanding). Use should be separated from knowledge. 3. In nonverbal skills; nonverbal problem-solving that does not require fine motor skills would be assessed separately from tasks that do, and tasks that are timed. 4.. Agreement across tests (whether past and present or present and present) is more important than minor differences across tests). Minor differences within normal ranges in most cases do not mean very much unless they represent very consistent patterns.
26 Services questions? Kinds of classes? Academic goals? Services? Extracurricular goals? Individualization/quality of life goals? (vocation/avocation) Pleasure Communication Engagement and motivation Exercise Areas of independence
27 Vocational strengths and weaknesses Tests like the TTAP; the Vineland, ABAS Academic achievement Problem solving Focus and independence Ways of communicating what he/she knows Rule out (for information purposes when someone has prompted, helped, reminds about numerical sign, encourages) though this may be necessary for access to services
28 Gastrointestinal Dysfunction Aggression Social Impairment Epilepsy- EEG abnormalities Sleep Disturbance ADHD Speech/ Motor problems: Communication Apraxia Deficits Language Disorders AUTISM SPECTRUM DISORDERS Intellectual Disabilities & Restricted Interests Social Anxiety OCD Disorder Immune Dysfunction
29 There is an increased risk for different psychiatric problems associated with ASD, which is not surprising. These include ADHD, anxiety disorders, depression, OCD and aggression. The best way to evaluate these behaviors is a combination of observation, parent and teacher report and self report if this is possible, just like everything else. Sometimes if there are concerns about these difficulties, additional observations are necessary. It is important not to let these concerns go unaddressed.
30 Mostly things are fine. Most hospitals just switched to ICD-10. We re concerned about what the UN will come up with for ICD-11. Usuable by primary care workers. Very quick diagnoses. Need to assert themselves. Different clinical and research versions. No talk yet, that I know, about DSM 5.1 but did just ask for agreements to participate in a review.
31 Individual differences In severity of ASD symptoms In families priorities, resources, needs In other aspects of development Importance of context in ASD symptoms Lack of biological markers and neurobiological diversity Availability of medical treatments that can have real effects on co-occurring conditions and other treatments that don t do much Lack of adequate funding for services and knowledge of what works for whom
32
33 How broad should diagnoses be? Can symptom counts work as well as more integrated systems in providing meaningful behavioral diagnoses or descriptions? Where does impairment fit in diagnostic criteria? What is the balance between requiring a carefully made but expensive diagnosis resulting in good sensitivity and specificity and having something cheap and quick with very poor specificity but available right away to all? What is the value of a diagnostic assessment? How does a diagnostic assessment contribute to caregiver and self understanding and treatment planning? How much do treatments need to be personalized versus how much can they be general? When do we need intensity and when do we need fine tuning?
34 CLINICAL OR PHENOTYPIC VARIABILITY Brain mechanisms??? Final common pathways leading to autistic outcomes ETIOLOGICAL VARIABILITY
35 Abrahams et al Nat Rev Genetics
36 Morena-De-Luca et al Lancet Neurology
37 >2 de novo LDF FDR= de novo LGD FDR=0.08 CHD8, SCN2A, DYRK1A, ANK2, GRIN2B, DSCAM, CHD2 ADNP, ANKRD11, ARID1B, DIP2A, FOXP1, GIGYF1, KATNAL2, KDM5B, KDM6B, BAZ2B, KMT2E (MLL5), MED13L. NCKAP1. PHF2. POGZ, RIMS1, TBR1. TCF7L2. TNRC6B, WAC, WDFY3 Iossifov, Rare O Roak, Sanders genes et al Nature associated (i2014) with autism
38 Krystal and State Cell 2014
39 Participant characteristics Mean z-scores by group None (n=1751) Sex/Age/NVIQ Matched Controls (n=113) Genetic Abnormalities dnlof or dncnv* (n=113) N Male (%) 1546 (88%) 86 (76%) 86 (76%) Age (mos) ± ± ±39.82 NVIQ 86.28± ± ±24.20 *FDR<.1; Sanders et al., 2015 *all variables were z-normalized using the Mean & SD of the full SSC sample.
40 Fusiform regions of interest Regions for each hemisphere (red) are shown on the total area of all regions (white) at x = 39, y = -46, z = (middle), using the clusters of hypoactivation in the ASD group (bottom). Right and left are reversed by convention. Coutanche MN, Thompson-Schill SL, Schultz RT. Multi-voxel pattern analysis of fmri data predicts clinical symptom severity. Neuroimage Jul 1;57(1): doi: /j.neuroimage Epub 2011 Apr 13. PMID:
41 DSM5 criteria provide a way to communicate and a framework for conveying information They are a beginning but not everything
42 Social Communication Deficits Autism Spectrum Disorders Repetitive Behaviors & Restricted Interests Sense of humor Fine motor skills Predictability Intelligence Visual-spatial skills Language Disorders Intellectual Disabilities Curiosity Attention to detail Honesty
43
44 Thank you for listening and thanks to all the patients and parents and clinicians who allowed us to work with them and show you these examples. Center for Autism and the Developing Brain (CADB) New York Presbyterian Hospital Westchester;
45 Decision Making Process NSE (20%* of UMACC referrals): Unlikely to receive ASD classification by another measure (ADI-R) Consider other clinical information Not ASD: Continue assessment considering other diagnoses ADOS Less decisive scores (28%* of UMACC referrals) Administer ADI-R or other instruments Working Diagnosis of ASD Not ASD PSE or High Specificity Score (52% of UMACC referrals): Likely to receive ASD classification by another measure (ADI-R) Consider other clinical information Working diagnosis of ASD NSE: Negative Screening Estimates; PSE: Positive Screening Estimates
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